Setdb2 controls convergence and extension movements during zebrafish gastrulation by transcriptional regulation of dvr1

Du, T.T., Xu, P.F., Dong, Z.W., Fan, H.B., Jin, Y., Dong, M., Chen, Y., Pan, W.J., Ren, R.B., Liu, T.X., Deng, M., Huang, Q.H.
Developmental Biology   392(2): 233-44 (Journal)
Registered Authors
Chen, Yi, Deng, Min, Dong, Mei, Jin, Yi, Liu, Ting Xi, Pan, Weijun, Xu, Peng-Fei
TGF-β superfamily, Zebrafish, convergence and extension, dvr1, histone methylation, setdb2
MeSH Terms
  • Animals
  • Blotting, Western
  • Cell Movement/physiology*
  • Fluorescent Antibody Technique
  • Gastrulation/physiology*
  • Gene Expression Regulation, Developmental/physiology*
  • Gene Knockdown Techniques
  • Histone-Lysine N-Methyltransferase/metabolism
  • Histone-Lysine N-Methyltransferase/physiology*
  • In Situ Hybridization
  • Microarray Analysis
  • Morpholinos/genetics
  • Real-Time Polymerase Chain Reaction
  • Transforming Growth Factor beta/genetics
  • Transforming Growth Factor beta/metabolism*
  • Zebrafish/embryology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Zebrafish Proteins/physiology*
24892953 Full text @ Dev. Biol.
As the primary driving forces of gastrulation, convergence and extension (C&E) movements lead to a medio-lateral narrowing and an anterior-posterior elongation of the embryonic body axis. Histone methylation as a post-translational modification plays a critical role in early embryonic development, but its functions in C&E movements remain largely unknown. Here, we show that the setdb2-dvr1 transcriptional cascade plays a critical role in C&E movements during zebrafish gastrulation. Knockdown of Setdb2, a SET domain-containing protein possessing a potential histone H3K9 methyltransferase activity, induced abnormal C&E movements, resulting in anterior-posterior shortening and medio-lateral expansion of the embryonic axis, as well as abnormal notochord cell polarity. Furthermore, we found that Setdb2 functions through fine-tuning the expression of dvr1, a ligand of the TGF-β superfamily, to an appropriate level to ensure proper C&E movements in a non-cell-autonomous manner. In addition, both overexpression and knockdown of Dvr1 at the one-cell stage resulted in defects at epiboly and C&E. These data demonstrate that Setdb2 is a novel regulator for C&E movements and acts by modulating the expression level of dvr1, suggesting that Dvr1 acts as a direct and essential mediator for C&E cell movements.
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Human Disease / Model
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